To investigate the relationship between farming exposures and asthma, we have developed a case-cohort study within a large cohort of farmers -- the Agricultural Health Study. This study follows up findings regarding the association between correlates of exposure to pathogen associated molecular patterns (such as endotoxin) and various questionnaire-based asthma and atopy phenotypes. It is also designed to follow-up findings based on questionnaire data of positive associations between pesticide exposures, especially organophospates, and questionnaire-based asthma phenotypes. To confirm and better understand these associations, objective measures of asthma and atopy phenotype are needed along with more detailed and objective exposure assessment. After obtaining scientific review for the proposal, in the past year, we have developed the protocol for this case-cohort study of asthma nested within the Agricultural Health Study. Human subjects approval has been obtained and study questionnaires, laboratory protocols and standard operating procedures have been developed. We plan to begin staff training early in FY2009 and begin subject enrollment shortly thereafter. This study builds upon the Agricultural Health Study, a large cohort of farmers and their spouses in Iowa and North Carolina. For case and noncase identification, we are using the third wave of questionnaire follow-up ongoing in the larger study. Our asthma add-on study involves making home visits with objective measures of exposure and asthma and allergy phenotypes on approximately 1,700 asthma cases and a random sample of the cohort as a comparison group (case-cohort design).